title: Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study.
abstract: Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. We analyzed data from a prospective nested case-control study among 662 incident colon cancer cases matched within risk sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. The percent effect change and corresponding CIs were estimated after adjusting for biomarkers shown to be associated with colon cancer risk. After multivariable adjustment, WC was associated with colon cancer risk in men (top vs. bottom tertile RR 1.68, 95% CI 1.06-2.65; ptrend  = 0.02) and in women (RR 1.67, 95% CI 1.09-2.56; ptrend  = 0.03). BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37-57%) of the association in men and 50% (95% CI 40-65%) of the association in women. Similar results were observed for the associations with BMI in men. These data suggest that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk.
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
authors.forename: Krasimira
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authors.lastname: Aleksandrova
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authors.forename: Kim
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authors.lastname: Tjønneland
authors.forename: Jytte
authors.initials: J
authors.lastname: Halkjaer
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: Françoise
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authors.lastname: Clavel-Chapelon
authors.forename: Annekatrin
authors.initials: A
authors.lastname: Lukanova
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Pavlos
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authors.lastname: Vidalis
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: Claudia
authors.initials: C
authors.lastname: Agnoli
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Genevieve
authors.initials: G
authors.lastname: Buckland
authors.forename: José-Juan
authors.initials: JJ
authors.lastname: Sánchez-Cruz
authors.forename: Miren
authors.initials: M
authors.lastname: Dorronsoro
authors.forename: María José Tormo
authors.initials: MJ
authors.lastname: Díaz
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: J
authors.initials: J
authors.lastname: Ramon Quiros
authors.forename: Petra H
authors.initials: PH
authors.lastname: Peeters
authors.forename: Anne M
authors.initials: AM
authors.lastname: May
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Richard
authors.initials: R
authors.lastname: Palmqvist
authors.forename: Francesca L
authors.initials: FL
authors.lastname: Crowe
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Nickolas
authors.initials: N
authors.lastname: Wareham
authors.forename: Tobias
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authors.lastname: Pischon
mesh_terms: D050154:Adiposity; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000097:blood / Q000453:epidemiology*; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor
keywords: adiposity; body mass index; colon cancer; mediating biomarkers; waist circumference